Tumor cell plasticity in endometrioid carcinoma is regulated by neuronal membrane glycoprotein M6‑b

Kusumoto,Shinya; Ikeda,Jun-Ichiro; Kurashige,Masako; Maeno‑Fujinami,Etsuko; Tahara,Shinichiro; Matsui,Takahiro; Nojima,Satoshi; Okuzaki,Daisuke; Morii,Eiichi

doi:10.3892/ol.2022.13631

February-2023 Volume 25 Issue 2

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February-2023 Volume 25 Issue 2

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Article

Tumor cell plasticity in endometrioid carcinoma is regulated by neuronal membrane glycoprotein M6‑b

Authors:
- Shinya Kusumoto
- Jun-Ichiro Ikeda
- Masako Kurashige
- Etsuko Maeno‑Fujinami
- Shinichiro Tahara
- Takahiro Matsui
- Satoshi Nojima
- Daisuke Okuzaki
- Eiichi Morii
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Affiliations: Department of Pathology, Osaka University Graduate School of Medicine, Suita, Osaka 565‑0871, Japan, Department of Diagnostic Pathology, Chiba University Graduate School of Medicine, Chiba 260‑8670, Japan, Single Cell Genomics, Human Immunology, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565‑0871, Japan
Article Number: 45
|
Published online on: December 14, 2022

https://doi.org/10.3892/ol.2022.13631
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Abstract

Tumor cell plasticity and tumor heterogeneity are involved in therapy resistance. Cancer stem cells (CSCs) refer to tumor cells that have the ability to self‑renew, and generate the diverse cells that comprise the tumor and complicate tumor heterogeneity. In recent years, CSCs have been reported to emerge from non‑CSCs, which is known as tumor cell plasticity; however, the mechanism has not been fully elucidated. The present study investigated tumor cell plasticity from the viewpoint of aldehyde dehydrogenase 1 family member A1 (ALDH1A1) activity, which is one of the markers of CSCs. In the endometrioid carcinoma cell line HEC‑1B, the ALDH1A1‑low population spontaneously yielded an ALDH1A1‑high population, mimicking tumor cell plasticity, and it was revealed that the mixture of the ALDH1A1‑high population with the ALDH1A1‑low population sometimes accelerated the transition from an ALDH1A1‑low to ALDH1A1‑high population. Two distinct HEC‑1B sublines were established. One of the two sublines accelerated such a transition and the other did not show such acceleration. In the former subline, the effect of the ALDH1A1‑high population was abolished when the direct cell‑cell contact between ALDH1A1‑high and ALDH1A1‑low populations was inhibited. By comparing the two sublines, the neuronal membrane glycoprotein M6‑b (GPM6B) was identified as the candidate mediating tumor cell plasticity. GPM6B was expressed in the border of ALDH1A1‑expressing tumor cells and non‑expressing tumor cells in clinical samples of EC. Notably, knockout of GPM6B decreased ALDH1A1 expression, whereas its overexpression increased the expression of ALDH1A1, suggesting that GPM6B mediated the induction of ALDH1A1 and the plasticity of CSCs.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Tumor cell plasticity in endometrioid carcinoma is regulated by neuronal membrane glycoprotein M6‑b

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